Head injury does not alter disease progression or neuropathologic outcomes in ALS

Abstract

Objectives: To study the effects of head injury on disease progression and on neuropathologic outcomes in amyotrophic lateral sclerosis (ALS).Methods: Patients with ALS were surveyed to obtain head injury history, and medical records were reviewed. Linear regression was performed to determine if head injury was a predictor for mean monthly decline of Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R), while controlling for confounders. Head injury history was obtained from family members of ALS autopsy cases. The frequency of tau proteinopathy, brain TDP-43 inclusions, and pathologic findings of Alzheimer disease (AD) were examined in ALS cases with head injury compared to cases without. Logistic regression was performed with each neuropathologic diagnosis as an outcome measure and head injury as a predictor variable. Results:No difference was seen in rate of decline of the ALSFRS-R between patients with head injury (n 5 24) and without (n 5 76), with mean monthly decline of 20.9 for both groups (p 5 0.18). Of 47 ALS autopsy cases (n 5 9 with head injury, n 5 38 without), no significant differences were seen in the frequency of tau proteinopathy (11% with head injury; 24% without), TDP-43 in the brain (44% with head injury; 45% without), or AD pathology (33% with head injury; 26% without). Independent logistic regression models showed head injury was not a predictor of tau pathology (p 5 0.42) or TDP-43 in the brain (p 5 0.99).Conclusions: Head injury was not associated with faster disease progression in ALS and did not result in a specific neuropathologic phenotype. The tau pathology described with chronic traumatic encephalopathy was found in ALS autopsy cases both with and without head injury. Head injury has been considered as a risk factor for amyotrophic lateral sclerosis (ALS), although epidemiologic studies on this topic yield mixed results 1-7 depending on the population studied and the ability to control for confounding variables. Recurrent head injuries can be associated with chronic traumatic encephalopathy (CTE), a condition clinically associated with dementia, parkinsonism, and behavior changes. Neuropathologic findings in CTE include tau-positive neurites, glia, and neurofibrillary tangles throughout the brain, particularly concentrated in cortical sulci and in perivascular regions. 8A 2010 neuropathologic study 9 described the autopsy findings of 12 professional athletes who experienced multiple head injuries and received a clinical diagnosis of CTE. Of the 12 athletes with CTE, 3 also had a clinical diagnosis of ALS. As expected, all 12 cases demonstrated the tau pathology described with CTE. Ten of the 12 cases demonstrated TDP-43 proteinopathy in the brain. The implications of this study have been debated, 10-12 but the authors proposed that head injury incites TDP-43 and tau-mediated neurotoxicity in certain vulnerable individuals, which can cause an ALS phenotype and accelerate neurodegeneration. If this hypothesis is true,

Prevalence of potential sports‐associated risk factors in Swiss amyotrophic lateral sclerosis patients

“…Indeed, in our cohort a history of head/neck injuries was linked to younger age at symptom onset (54.1 vs. 61.8 years, p = .013). This, however, contrasts previous observations that a single head trauma is not associated with age at symptom‐onset and the rate of disease progression (Fournier, Gearing, Upadhyayula, Klein, & Glass, ). Noteworthy, about half of our patients with a history of head/neck injury reported more than one event and for analysis we pooled patients with one or more head/neck injuries.…”

Role of NMDA Receptor-Mediated Glutamatergic Signaling in Chronic and Acute Neuropathologies

“…In this study, a linear regression was performed to determine if head injury was a predictor for the mean monthly decline of ALS using the Functional Rating Scale-Revised (ALSFRS-R) [229]. In this study, 24 ALS patients with TBI and 76 ALS control patients were compared.…”

Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank

“…Subsets of patients with CTE have amyloid-β, TDP-43 or α-synuclein pathology [16, 23, 31, 32]. CTE pathology has also been reported in patients with amyotrophic lateral sclerosis (ALS) [7]. TDP-43 pathology is detected in up to 80% of CTE cases, and pathologically confirmed ALS is reported in approximately 12% of CTE cases [15, 22, 23].…”